Attention during the past year has focused on the structure and function of proteins in the normal lens and in cataractogenesis. Dr. Peter Frederikse has developed evidence that proteins in the nuclear (central) region of the normal lens assume an amyloid type structure. This highly ordered "crossed beta-sheet" structure may be crucial to the functional integrity of the lens by providing the high degree of stability necessary to maintain transparency in the cells of the lens nucleus which remain for the life of the individual and have lost the capacity to synthesize protein. Dr. Frederikse also has generated evidence suggesting that inappropriate or excessive formation of amyloid may be involved in cataract formation. Dr. Vasanth Rao has demonstrated the presence in the lens of various members of the ras family of small GTPases. These proteins are involved in signal transduction pathways which regulate critical cellular processes including proliferation, differentiation and apoptosis. Dr. Rao has produced experimental evidence supporting the hypothesis that cataracts induced in animals by certain cholesterol-lowering agents are actually caused by inactivation of these small GTPases. Recent efforts have concentrated on the role of one family of small GTPases called Rho. By using a bacterial toxin which specifically inactivates Rho, it has been shown that Rho is crucial to controlling proliferation of lens cells in culture and that its inactivation causes organ-cultured lenses to become cataractous. A transgenic mouse which is a lens-specific "functional knockout" of Rho has been engineered and exhibits cataracts. Studies are underway to elucidate the mechanisms responsible for the lens opacification in these animals. In studies with collaborators at the University of Illinois we have identified the first enzyme/crystallin present in a primate lens. The enzyme betaine-homocysteine methyltransferase (BHMT) is a major protein in the rhesus monkey lens, particularly in those lens fibers formed during embryonic development. Expression of BHMT is markedly down-regulated in the lens fibers generated later in life. The enzyme is catalytically active but at this point it is uncertain whether its function in the lens relates to its enzymatic activity or to some other property of the protein.